Statistically significant decreased levels of cyclic AMP and increased levels of cyclic GMP were observed in psoriasis lesions versus uninvolved epidermis. The causes of these changes are being investigated at the present time. There appears to be an increased Km and Vmax for the soluble cyclic phosphodiesterase (PDE) that is present in the lesion cells as compared to the uninvolved epidermal enzyme. In vitro experiments in other tissues have demonstrated that cyclic GMP can increase the rate of hydrolysis of cyclic AMP by PDE. Therefore, the altered kinetic properties of the PDE plus the increased levels of cyclic GMP may account for the decreased cyclic AMP levels in vivo. The possibility of increased diffusion of cyclic AMP out of the lesional cells is also being determined. Preliminary data would indicate that the diffusion rate of cyclic AMP into the medium is the same for both the lesion and uninvolved epidermis. These studies are being expanded to cover several time points in order to eliminate diffusion as the reason for decreased cyclic AMP levels in the lesion. Cyclic AMP elevating agents are being tested in double blind clinical trials in order to help establish the decreased cyclic AMP levels as being important to the pathology of psoriasis.